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Publication : Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration.

First Author  Ryu S Year  2013
Journal  Cancer Cell Volume  23
Issue  1 Pages  63-76
PubMed ID  23328481 Mgi Jnum  J:194343
Mgi Id  MGI:5473459 Doi  10.1016/j.ccr.2012.11.019
Citation  Ryu S, et al. (2013) Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Cancer Cell 23(1):63-76
abstractText  The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.
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